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1.
J Biol Chem ; 300(2): 105591, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38141769

RESUMO

Long noncoding RNAs (lncRNAs) are specifically expressed in different diseases and regulate disease progression. To explore the functions of rheumatoid arthritis (RA)-specific lncRNA, we determined the lncRNA expression profile of fibroblast-like synoviocytes (FLS) obtained from patients with RA and osteoarthritis (OA) using a LncRNA microarray and identified up-regulated LncNFYB in RA as a potential therapeutic target. Using gain- and loss-of-function studies, LncNFYB was proven to promote FLS proliferation and cell cycle progress but not affect their invasion, migration, and apoptotic abilities. Further investigation discovered that LncRNA could combine with annexin A2 (ANXA2) and enhance the level of phospho-ANXA2 (Tyr24) in the plasma membrane area, which induced the activation of ERK1/2 to promote proliferation. These findings provide new insights into the biological functions of LncNFYB on modification of FLS, which may be exploited for the therapy of RA.


Assuntos
Anexina A2 , Artrite Reumatoide , Sistema de Sinalização das MAP Quinases , RNA Longo não Codificante , Sinoviócitos , Humanos , Anexina A2/genética , Anexina A2/metabolismo , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/fisiopatologia , Proliferação de Células/genética , Células Cultivadas , Ativação Enzimática/genética , Fibroblastos/citologia , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Osteoartrite/genética , Osteoartrite/metabolismo , Osteoartrite/fisiopatologia , Fosforilação/genética , Ligação Proteica/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Sinoviócitos/citologia , Sinoviócitos/metabolismo
3.
Sci Rep ; 13(1): 1304, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693893

RESUMO

The aim of this study was to clarify the effect of climatic environment on the immunological features of rheumatoid arthritis (RA). Blood samples were collected from patients with RA and healthy controls (HCs), matched by age and sex, living in two locations, Tsukuba and Karuizawa, which differ in their altitude and average air temperature and atmospheric pressure. Analysis of peripheral blood mononuclear cells (PBMCs) revealed that the proportion of T and B cell subpopulations in HCs and RA patients were significantly different between two sites. Inverse probability weighting adjustment with propensity scores was used to control for potential confounding factors. The results revealed that, in comparison with RA patients in Tsukuba, those in Karuizawa showed a significant increase in cTh1, cTfh1, and Tph cells, and significant decrease in cTh17, cTh17.1, and CD8+ Treg in T cell subpopulations, and a significant increase in DNB, DN1, DN2, and class-switched memory B cells, and a significant decrease in unswitched memory B, naïve B cells, and ABCs in B cell subpopulations. Our results suggest the possibility that climatic environment might have an effect on immune cell proportion and function, and be related to the pathogenic mechanism of RA.


Assuntos
Artrite Reumatoide , Meio Ambiente , Leucócitos Mononucleares , Humanos , Artrite Reumatoide/imunologia , Artrite Reumatoide/fisiopatologia , Linfócitos B/imunologia , Leucócitos Mononucleares/imunologia , Linfócitos T/imunologia
4.
South Med J ; 115(2): 125-128, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35118501

RESUMO

OBJECTIVES: Recombinant zoster vaccine (RZV) is Food and Drug Administration approved for the prevention of herpes zoster (shingles) in adults 50 years old and older. Immunocompromised subjects were excluded from the pivotal vaccine trials. We studied the safety of this vaccine in our university-affiliated rheumatology practice. METHODS: This was a single-center, retrospective study focusing on subjects who received RZV during 2018. We collected the demographic data, any self-reported adverse events after vaccination, C-reactive protein, Routine Assessment of Patient Index Data 3 (RAPID3) scores for subjects with rheumatoid arthritis, and available RAPID3 scores for all study subjects before and after the vaccination. RESULTS: Comparision of C-reactive protein (n = 40), RAPID3 scores for subjects with rheumatoid arthritis (n = 16), and available RAPID3 scores for all subjects (n = 21) using the paired t test, did not show significant differences before and after the administration of RZV. A total of 6.4% of patients reported adverse events after vaccination. The adverse events were mild and did not lead to hospitalization, end organ damage, or change in treatment plan. CONCLUSIONS: The RZV was safe and well tolerated among our study population.


Assuntos
Artrite Reumatoide/complicações , Herpes Zoster/tratamento farmacológico , Segurança do Paciente/normas , Vacinas Sintéticas/efeitos adversos , Adulto , Idoso , Artrite Reumatoide/fisiopatologia , Herpes Zoster/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Reumatologia/métodos , Reumatologia/estatística & dados numéricos , Vacinas Sintéticas/uso terapêutico
5.
Int J Mol Sci ; 23(3)2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35163173

RESUMO

Pain, fatigue, and physical activity are major determinants of life quality in rheumatoid arthritis (RA). Janus kinase (JAK) inhibitors have emerged as effective medications in RA and have been reported to exert direct analgesic effect in addition to reducing joint inflammation. This analysis aims to give an extensive summary of JAK inhibitors especially focusing on pain and patient reported outcomes (PRO). MEDLINE, CENTRAL, Embase, Scopus, and Web of Science databases were searched on the 26 October 2020, and 50 randomized controlled trials including 24,135 adult patients with active RA met the inclusion criteria. JAK inhibitors yielded significantly better results in all 36 outcomes compared to placebo. JAK monotherapy proved to be more effective than methotrexate in 9 out of 11 efficacy outcomes. In comparison to biological disease-modifying antirheumatic drugs, JAK inhibitors show statistical superiority in 13 of the 19 efficacy outcomes. Analgesic effect determined using the visual analogue scale and American College of Rheumatology (ACR) 20/50/70 response rates was significantly greater in the JAK group in all comparisons, and no significant difference regarding safety could be explored. This meta-analysis gives a comprehensive overview of JAK inhibitors and provides evidence for their superiority in improving PROs and disease activity indices in RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/fisiopatologia , Bases de Dados Factuais , Humanos , Inibidores de Janus Quinases/farmacologia , Janus Quinases/metabolismo , Metotrexato/uso terapêutico , Dor/tratamento farmacológico , Manejo da Dor/métodos , Medidas de Resultados Relatados pelo Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
6.
Comput Math Methods Med ; 2022: 6244175, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35222687

RESUMO

BACKGROUND: Researches have confirmed that the abnormal signals of OX40 and PD-1 lead to the changes of T cell biological behavior, thus participating the immunopathological process of RA. However, the pathogenesis of RA immunopathological process has not been clarified yet. METHODS: 30 DBA/1 mice were randomly divided into 5 groups (6 mice per group): control group, collagen-induced arthritis (CIA) group, PD-1-Fc/CIA group, OX40-Fc/CIA group, and PD-1-Fc + OX40-Fc/CIA group. The pathological changes in mice joints were observed by H&E staining. The proportion of CD4+ T, CD8+ T, CD28+, and CD19+ cells in peripheral blood mononuclear cells (PBMCs) was detected by flow cytometry. Serum inflammatory factors (CRP, IL-2, IL-4, IL-1ß, INF-γ) and bone metabolism-related genes (CTX-I, TRACP-5b, BALP) were detected by ELISA assay. Western blotting was applied to measure the NF-κB signaling pathway-related protein (p-IKKß, p-IκBα, p50) expression in synovial tissue of mice joint. RESULTS: Compared with the control group, CIA mice showed significant increases in arthritis score and pathological score. In the CIA group, a marked decrease was identified in the proportion of CD8+ T, CD19+, and CD68+ cells. Additionally, the CIA group was associated with upregulation of secretion of inflammatory factors in serum and expression of bone metabolism-related genes and NF-κB pathway-related proteins. Compared with the CIA group, the same indexes above showed a further aggravation in the PD-1-Fc group while all indexes improved in the OX40-Fc group. Besides, OX40-Fc fusion protein slowed down significantly the further deterioration of CIA mouse pathological process caused by PD-1-Fc fusion protein. CONCLUSION: OX40-Fc fusion protein alleviates PD-1-Fc-aggravated RA by inhibiting inflammatory response. This research provides biological markers with clinical significance for diagnosis and prognosis of RA, as well as offers theoretical and experimental foundation to the new targets for immune intervention.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptores OX40/uso terapêutico , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Experimental/fisiopatologia , Artrite Reumatoide/patologia , Artrite Reumatoide/fisiopatologia , Biomarcadores/metabolismo , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Colágeno Tipo I/metabolismo , Biologia Computacional , Humanos , Fragmentos Fc das Imunoglobulinas/imunologia , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/patologia , Inflamação/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos DBA , NF-kappa B/metabolismo , Peptídeos/metabolismo , Receptor de Morte Celular Programada 1/imunologia , Receptores OX40/imunologia , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Fosfatase Ácida Resistente a Tartarato/metabolismo
7.
J Clin Lab Anal ; 36(1): e24112, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34788483

RESUMO

OBJECTIVE: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) participates in inflammatory and autoimmune diseases via activating various signaling pathways and promoting the differentiation of T-helper (Th) 1 and Th17 cells; however, it is rarely reported in rheumatoid arthritis (RA). This study aimed to assess the correlation of MALT1 with Th1 and Th17 cells and evaluate its potential as a biomarker for evaluating disease activity and treatment outcomes in RA patients. METHODS: This study enrolled 139 RA patients and 45 health controls (HCs); then, blood MALT1, Th1, and Th17 cells were determined. For RA patients only, blood MALT1 at week (W) 6 and W12 after treatment was also detected. Additionally, clinical response and remission of RA patients were assessed at W12. RESULTS: MALT1 (p < 0.001), Th1 (p = 0.011), and Th17 (p < 0.001) cells were all increased in RA patients than HCs; meanwhile, increased MALT1 was associated with elevated Th1 (p = 0.003) and Th17 (p < 0.001) cells in RA patients. Besides, MALT1, Th1, and Th17 cells were positively correlated with parts of disease activity indexes in RA patients (all p < 0.050). In addition, MALT1 was gradually declined from W0 to W12 (p < 0.001) in RA patients. Specifically, MALT1 at W6 and W12 was lower in response patients than no response patients (both p < 0.010), also in remission patients than no remission patients (both p < 0.050). CONCLUSION: MALT1, Th1, and Th17 cells are dysregulated, inter-correlated, and correlated with disease activity in RA patients; meanwhile, the decline of MALT1 expression can partly reflect RA treatment response and remission.


Assuntos
Artrite Reumatoide , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa , Células Th1/metabolismo , Células Th17/metabolismo , Adulto , Idoso , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/sangue , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/metabolismo , Estudos Prospectivos , Resultado do Tratamento
8.
Emerg Med Clin North Am ; 40(1): 179-191, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34782087

RESUMO

Systemic lupus erythematosus and rheumatoid arthritis are just 2 of several autoimmune connective tissue diseases that are primarily chronic in nature but can present to the emergency department by virtue of an acute exacerbation of disease. Beyond an acute exacerbation of disease, their predilection for invading multiple organ systems lends itself to the potential for patients presenting to the emergency department with either a single or isolated symptom or a myriad of signs and/or symptoms indicative of a degree of disease complexity and severity that warrant timely recognition and resuscitation.


Assuntos
Artrite Reumatoide/fisiopatologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/terapia , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia
9.
Rheumatol Int ; 42(2): 241-250, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34846554

RESUMO

The COVID-19 pandemic and social distancing restrictions have significantly reduced population-wide physical activity (PA) levels. However, the impact of the pandemic and relevant restrictions on PA participation, and any potential barriers to it, in people with rheumatoid arthritis (RA) are not clear. Furthermore, we are unsure if any such PA changes have affected their body weight, mental wellbeing, and/or quality of life (QoL). Thus, the aim of this study was to examine the impact of the lockdown on PA participation in people with RA, versus people without RA. Participants (n = 128; RA = 27, non-RA = 101) completed a self-administered online survey, which included questions on PA, body weight, mental wellbeing and QoL. PA participation during lockdown was significantly lower among RA versus non-RA participants (p < 0.001). Additionally, a similar profile of results was found where more RA participants vs non-RA participants reported reduced habitual PA (59% vs 33%) and increased body weight (59% vs 35%). Mental wellbeing scores were similarly low in both groups during lockdown (RA: 20.8 ± 4.2; non-RA: 22.2 ± 3.4, p = 0.080). Matched group comparisons identified similar trends to full sample analyses. In the first months of the lockdown, more people with RA reported decreased PA participation and increased body weight than their non-RA counterparts. Access to exercise equipment and facilities appears to be the main cause for these results. Looking beyond COVID-19, specific PA promotion for people with RA will be required to prevent a pandemic of inactivity.


Assuntos
Artrite Reumatoide/fisiopatologia , COVID-19/prevenção & controle , Exercício Físico/estatística & dados numéricos , Quarentena , Adulto , Artrite Reumatoide/psicologia , Peso Corporal , Estudos de Casos e Controles , Dibenzocicloeptenos , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Qualidade de Vida , SARS-CoV-2 , Reino Unido , Adulto Jovem
10.
Cardiovasc Res ; 118(1): 254-266, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33483748

RESUMO

AIMS: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting joints and blood vessels. Despite low levels of low-density lipoprotein cholesterol (LDL-C), RA patients exhibit endothelial dysfunction and are at increased risk of death from cardiovascular complications, but the molecular mechanism of action is unknown. We aimed in the present study to identify the molecular mechanism of endothelial dysfunction in a mouse model of RA and in patients with RA. METHODS AND RESULTS: Endothelium-dependent relaxations to acetylcholine were reduced in aortae of two tumour necrosis factor alpha (TNFα) transgenic mouse lines with either mild (Tg3647) or severe (Tg197) forms of RA in a time- and severity-dependent fashion as assessed by organ chamber myograph. In Tg197, TNFα plasma levels were associated with severe endothelial dysfunction. LOX-1 receptor was markedly up-regulated leading to increased vascular oxLDL uptake and NFκB-mediated enhanced Arg2 expression via direct binding to its promoter resulting in reduced NO bioavailability and vascular cGMP levels as shown by ELISA and chromatin immunoprecipitation. Anti-TNFα treatment with infliximab normalized endothelial function together with LOX-1 and Arg2 serum levels in mice. In RA patients, soluble LOX-1 serum levels were also markedly increased and closely related to serum levels of C-reactive protein. Similarly, ARG2 serum levels were increased. Similarly, anti-TNFα treatment restored LOX-1 and ARG2 serum levels in RA patients. CONCLUSIONS: Increased TNFα levels not only contribute to RA, but also to endothelial dysfunction by increasing vascular oxLDL content and activation of the LOX-1/NFκB/Arg2 pathway leading to reduced NO bioavailability and decreased cGMP levels. Anti-TNFα treatment improved both articular symptoms and endothelial function by reducing LOX-1, vascular oxLDL, and Arg2 levels.


Assuntos
Aorta Torácica/efeitos dos fármacos , Arginase/metabolismo , Artrite Reumatoide/tratamento farmacológico , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Receptores Depuradores Classe E/metabolismo , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Vasodilatação/efeitos dos fármacos , Adulto , Animais , Animais Geneticamente Modificados , Aorta Torácica/enzimologia , Aorta Torácica/imunologia , Aorta Torácica/fisiopatologia , Arginase/genética , Artrite Reumatoide/enzimologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/fisiopatologia , Estudos de Casos e Controles , Modelos Animais de Doenças , Células Endoteliais/enzimologia , Células Endoteliais/imunologia , Endotélio Vascular/enzimologia , Endotélio Vascular/imunologia , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Lipoproteínas LDL/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Receptores Depuradores Classe E/genética , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética
11.
Arthritis Care Res (Hoboken) ; 74(3): 493-500, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-32886866

RESUMO

OBJECTIVE: To determine whether patients with inflammatory joint disease (IJD) meet current guidelines on physical activity, and to determine which factors influence physical activity levels and sedentary behavior (SB) in patients with IJD. METHODS: This was a cross-sectional study of 137 patients with a medical diagnosis of an IJD prior to commencing an NHS-run inflammatory arthritis exercise program. Physical activity and SB were measured objectively using a thigh-worn physical activity monitor for 7 consecutive days. Activity levels were subdivided into low physical activity (LPA) and moderate-to-vigorous physical activity (MVPA). First, activity levels were analyzed against current guidelines of 150 minutes of MVPA per week. Second, time spent in SB, LPA, and MVPA was analyzed against possible determinants. RESULTS: In total, 29% of patients with IJD met current physical activity guidelines. Patients on average spent 10 hours per day in SB. Poor physical fitness measured by the 6-minute walk test was the only significant predictor (P = 0.019) of high SB (R2  = 4.7%). Attending an exercise facility in the community (P = 0.034) and low role limitations due to physical health (P = 0.008) predicted high levels of LPA, following a backward multiple regression (R2  = 8.0%). Low role limitations due to emotional problems (P = 0.031), higher physical fitness (P = 0.002), and healthier exercise attitudes and beliefs (P = 0.021) predicted meeting current physical activity guidelines, following a backward conditional logistic regression, explaining between 22.2% and 31.7% of variance. CONCLUSION: Patients with IJD are inactive and spent much time in SB. Good general health predicts high activity levels. No disease-specific factors were found to determine SB, LPA, or MVPA.


Assuntos
Artrite Reumatoide/fisiopatologia , Exercício Físico , Comportamento Sedentário , Espondilartrite/fisiopatologia , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Rheumatology (Oxford) ; 61(2): 679-687, 2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33905483

RESUMO

OBJECTIVE: To identify the clinical and biomechanical characteristics associated with falls in people with RA. METHODS: A total of 436 people ≥60 years of age with RA completed a 1 year prospective survey of falls in the UK. At baseline, questionnaires recorded data including personal and medical history, pain and fatigue scores, health-related quality of life (HRQoL), physical activity and medication history. The occurrence of falls wasmonitored prospectively over 12 months by monthly self-reporting. A nested sample of 30 fallers (defined as the report of one or more falls in 12 months) and 30 non-fallers was evaluated to assess joint range of motion (ROM), muscle strength and gait parameters. Multivariate regression analyses were undertaken to determine variables associated with falling. RESULTS: Compared with non-fallers (n = 236), fallers (n = 200) were older (P = 0.05), less likely to be married (P = 0.03), had higher pain scores (P < 0.01), experienced more frequent dizziness (P < 0.01), were frequently taking psychotropic medications (P = 0.02) and reported lower HRQoL (P = 0.02). Among those who underwent gait laboratory assessments, compared with non-fallers, fallers showed a greater anteroposterior (AP; P = 0.03) and medial-lateral (ML) sway range (P = 0.02) and reduced isokinetic peak torque and isometric strength at 60° knee flexion (P = 0.03). Fallers also showed shorter stride length (P = 0.04), shorter double support time (P = 0.04) and reduced percentage time in swing phase (P = 0.02) and in knee range of motion through the gait cycle (P < 0.01). CONCLUSION: People with RA have distinct clinical and biomechanical characteristics that place them at increased risk of falling. Assessment for these factors may be important to offer more targeted rehabilitation interventions.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Artrite Reumatoide/complicações , Idoso , Artrite Reumatoide/patologia , Artrite Reumatoide/fisiopatologia , Fenômenos Biomecânicos , Estudos de Casos e Controles , Feminino , Marcha , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Força Muscular , Gravidade do Paciente , Estudos Prospectivos , Qualidade de Vida , Amplitude de Movimento Articular , Análise de Regressão , Fatores de Risco , Inquéritos e Questionários
13.
J Ethnopharmacol ; 283: 114657, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34600080

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Daphnes Cortex (Daphne Giraldii Nitsche, DGN) is a popular traditional Chinese herbal medicine for traumatic injuries and rheumatoid arthritis (RA) in the Shaanxi and Gansu provinces of China. Due to skin irritation caused by raw DGN (RDGN), licorice-processed DGN products are usually used in clinical practice. However, the efficacy and mechanisms of action between DGN and its licorice-processed DGN products in treating RA have not been compared. AIMS: This study compared the efficacy and elucidated the mechanisms in vitro and in vivo between RDGN and its licorice-processed DGN products in treating RA. MATERIALS AND METHODS: A collagen-induced RA rat model was established, and treated with different doses of RDGN and its licorice-processed DGN products for 4 weeks to explore the therapeutic effects. The anti-inflammatory effects were assessed in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). Analyses of the differential quality markers (DQMs) between DGN and its licorice-processed DGN products using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and non-targeted metabolomics analyses of rat synovial tissues were used to systematically explore correlations between DGN processing and its efficacy. RESULTS: Licorice-processed DGN products significantly ameliorated RA symptoms in CIA rats. Licorice-processed DGN products also regulated inflammatory cytokines, matrix metalloproteinases, and vascular endothelial growth factor in the serum and cell supernatants. Licorice-processed DGN products significantly inhibited Toll-like receptor 4/nuclear factor kappa B/NOD-like receptor family, pyrin domain containing 3 (TLR4/NF-κB/NLRP3) signaling in CIA rats and LPS-induced RAW264.7 cells. The DQMs between RDGN and its licorice-processed DGN products were identified, most of which were amino acids or energy-related metabolites present in licorice-processed DGN products. Correlations between DQMs with differential metabolites and differential metabolic pathways were established. CONCLUSIONS: Licorice-processed DGN products displayed better anti-inflammatory effects via the TLR4/NF-κB/NLRP3 signaling pathway on CIA rats and LPS-induced RAW264.7 cells, and regulation of the metabolic profile in treating RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Daphne/química , Glycyrrhiza/química , Inflamação/tratamento farmacológico , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/fisiopatologia , Artrite Reumatoide/fisiopatologia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Inflamação/fisiopatologia , Lipopolissacarídeos , Masculino , Camundongos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo
14.
Biomed Res Int ; 2021: 9774980, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34901282

RESUMO

OBJECTIVE: Rheumatoid arthritis (RA) causes progressive changes in the musculoskeletal system compromising neuromuscular control especially in the hands. Whole-body vibration (WBV) could be an alternative for the rehabilitation in this population. This study investigated the immediate effect of WBV while in the modified push-up position on neural ratio (NR) in a single session during handgrip strength (HS) in women with stable RA. METHODS: Twenty-one women with RA (diagnosis of disease: ±8 years, erythrocyte sedimentation rate: ±24.8, age: 54± 11 years, BMI: 28 ± 4 kg·m-2) received three experimental interventions for five minutes in a randomized and balanced cross-over order: (1) control-seated with hands at rest, (2) sham-push-up position with hands on the vibration platform that remained disconnected, and (3) vibration-push-up position with hands on the vibration platform turned on (45 Hz, 2 mm, 159.73 m·s-2). At the baseline and immediately after the three experimental interventions, the HS, the electromyographic records (EMGrms), and range of motion (ROM) of the dominant hand were measured. The NR, i.e., the ratio between EMGrms of the flexor digitorum superficialis (FDS) muscle and HS, was also determined. The lower NR represented the greater neuromuscular efficiency (NE). RESULTS: The NR was similar at baseline in the three experimental interventions. Despite the nonsignificance of within-interventions (p = 0.0611) and interaction effect (p = 0.1907), WBV exercise reduced the NR compared with the sham and control (p = 0.0003, F = 8.86, η 2 = 0.85, power = 1.00). CONCLUSION: Acute WBV exercise under the hands promotes neuromuscular modifications during the handgrip of women with stable RA. Thus, acute WBV exercise may be used as a preparatory exercise for the rehabilitation of the hands in this population. This trial is registered with trial registration 2.544.850 (ReBEC-RBR-2n932c).


Assuntos
Artrite Reumatoide/fisiopatologia , Exercício Físico/fisiologia , Força da Mão/fisiologia , Mãos/fisiopatologia , Força Muscular/fisiologia , Músculo Esquelético/fisiopatologia , Estudos Cross-Over , Eletromiografia/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Modalidades de Fisioterapia , Amplitude de Movimento Articular/fisiologia , Vibração
15.
PLoS One ; 16(12): e0260423, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34879087

RESUMO

Complete Freund's adjuvant (CFA) has been used to develop the arthritic or inflammatory condition in the animal, but there is a lack of information concerning high CFA doses on nociceptive behaviour and inflammatory parameters. This study aimed to compare the effects of different high doses of CFA in rat to closely mimic nociceptive and inflammatory parameters of rheumatoid arthritis (RA) in humans. Twenty-four male Sprague-Dawley rats were randomly divided into four groups (n = 6): Control (C), CFA-induced polyarthritic groups at 5.0 mg/mL (CFA 5.0), 7.5 mg/mL (CFA 7.5) and 10.0mg/mL (CFA 10.0). The rats' right hindpaw was inoculated with CFA intradermally and developed into a polyarthritic state within 20 days. Nociceptive behavioural assessments, including von Frey and hot plate tests and spontaneous activities, were conducted on day 0, 7, 15 and 20. Bilateral ankle joints diameter and circumference, full blood count, joints and paw histological examinations were also conducted throughout the study period. Based on the results, CFA 5.0 and CFA 7.5 groups showed a significant increase in spontaneous activities and development of thermal hyperalgesia but no change in body weight and food intake, no development of tactile allodynia and haematological indices, and no significant morphological changes of joints histology. Meanwhile, CFA 10.0 group demonstrated significant and constant changes in all nociceptive and inflammatory parameters investigated. In conclusion, CFA at the dose of 10mg/mL has the most potential and reliable dosage to develop polyarthritis in a rat model to mimic RA condition in humans.


Assuntos
Artrite Experimental/fisiopatologia , Artrite Reumatoide/fisiopatologia , Adjuvante de Freund/efeitos adversos , Nociceptividade/efeitos dos fármacos , Animais , Artrite Experimental/induzido quimicamente , Artrite Reumatoide/induzido quimicamente , Relação Dose-Resposta a Droga , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
16.
Isr Med Assoc J ; 23(11): 693-698, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34811983

RESUMO

BACKGROUND: In rheumatoid arthritis (RA), females usually have a worse prognosis. To date, the influence of physician gender in the evaluation of RA activity is still largely unknown. OBJECTIVES: To investigate the discrepancy in RA disease activity assessment between male and female physicians and to compare patient and evaluator perception of disease activity and global health (GH) status. METHODS: One female and one male rheumatologist evaluated 154 RA patients recording tender and swollen joint count, GH, evaluator global assessment (EGA), and patient global assessment (PGA) disease activity. A third rheumatologist calculated DAS28, CDAI, and SDAI. Difference was evaluated by Wilcoxon test. Physician-patient agreement was assessed by intraclass correlation coefficient. RESULTS: GH, PGA, and DAS28 were higher when recorded by the female examiner. Male EGA was higher than female. Among male patients, PGA was higher when collected by the female examiner. The probability of being judged as having an active disease did not rely on physician gender. The agreement with the physician's evaluation of disease activity was high. PGA values were higher than EGA in both examiners. The physician-patient agreement was moderate for the male examiner and good for the female. The female physician had a higher agreement with both genders. CONCLUSIONS: Subjective measure of disease activity differs between female and male rheumatologists, contributing to a different evaluation of disease activity. Patients have a higher perception of disease activity compared to physicians. The stronger agreement between female physicians and patients may be related to a more emphatic setting established by the female physician.


Assuntos
Artrite Reumatoide , Empatia , Relações Médico-Paciente , Médicas/psicologia , Avaliação de Sintomas , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/psicologia , Competência Clínica , Feminino , Indicadores Básicos de Saúde , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Administração dos Cuidados ao Paciente , Prognóstico , Índice de Gravidade de Doença , Fatores Sexuais , Avaliação de Sintomas/métodos , Avaliação de Sintomas/estatística & dados numéricos
17.
Cells ; 10(11)2021 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-34831081

RESUMO

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease of unknown etiology, primarily affecting the joints, then extra-articular manifestations can occur. Due to its complexity, which is based on an incompletely elucidated pathophysiological mechanism, good RA management requires a multidisciplinary approach. The clinical status of RA patients has improved in recent years due to medical advances in diagnosis and treatment, that have made it possible to reduce disease activity and prevent systemic complications. The most promising results were obtained by developing disease-modifying anti-rheumatic drugs (DMARDs), the class to which conventional synthetic, biologic, and targeted synthetic drugs belong. Furthermore, ongoing drug development has led to obtaining molecules with improved efficacy and safety profiles, but further research is needed until RA turns into a curable pathology. In the present work, we offer a comprehensive perspective on the management of RA, by centralizing the existing data provided by significant literature, emphasizing the importance of an early and accurate diagnosis associated with optimal personalized treatment in order to achieve better outcomes for RA patients. In addition, this study suggests future research perspectives in the treatment of RA that could lead to higher efficacy and safety profiles and lower financial costs.


Assuntos
Artrite Reumatoide/patologia , Artrite Reumatoide/terapia , Antirreumáticos/química , Antirreumáticos/uso terapêutico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/fisiopatologia , Humanos , Modelos Biológicos , Inibidores de Proteínas Quinases/uso terapêutico
18.
PLoS One ; 16(11): e0259574, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34758045

RESUMO

INTRODUCTION: Rheumatoid arthritis(RA) and osteoarthritis(OA) patients showed systemic manifestations that may lead to a reduction in muscle strength, muscle mass and, consequently, to a reduction in functionality. On the other hand, moderate intensity resistance training(MIRT) and high intensity resistance training(HIRT) are able to improve muscle strength and muscle mass in RA and OA without affecting the disease course. However, due to the articular manifestations caused by these diseases, these patients may present intolerance to MIRT or HIRT. Thus, the low intensity resistance training combined with blood flow restriction(LIRTBFR) may be a new training strategy for these populations. OBJECTIVE: To perform a systematic review with meta-analysis to verify the effects of LIRTBFR on muscle strength, muscle mass and functionality in RA and OA patients. MATERIALS AND METHODS: A systematic review with meta-analysis of randomized clinical trials(RCTs), published in English, between 1957-2021, was conducted using MEDLINE(PubMed), Embase and Cochrane Library. The methodological quality was assessed using Physiotherapy Evidence Database scale. The risk of bias was assessed using RoB2.0. Mean difference(MD) or standardized mean difference(SMD) and 95% confidence intervals(CI) were pooled using a random-effects model. A P<0.05 was considered statistically significant. RESULTS: Five RCTs were included. We found no significant differences in the effects between LIRTBFR, MIRT and HIRT on muscle strength, which was assessed by tests of quadriceps strength(SMD = -0.01[-0.57, 0.54], P = 0.96; I² = 58%) and functionality measured by tests with patterns similar to walking(SMD = -0.04[-0.39, 0.31], P = 0.82; I² = 0%). Compared to HIRT, muscle mass gain after LIRTBFR was reported to be similar. When comparing LIRTBFR with low intensity resistance training without blood flow restriction(LIRT), the effect LIRTBFR was reported to be higher on muscle strength, which was evaluated by the knee extension test. CONCLUSION: LIRTBFR appears to be a promising strategy for gains in muscle strength, muscle mass and functionality in a predominant sample of RA and OA women.


Assuntos
Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/terapia , Terapia de Restrição de Fluxo Sanguíneo/métodos , Hipertrofia/terapia , Força Muscular/fisiologia , Treinamento de Força , Hemodinâmica/fisiologia , Humanos , Hipertrofia/fisiopatologia
19.
Sci Rep ; 11(1): 21537, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728679

RESUMO

To evaluate the changes of left atrial (LA) geometry and function in patients with rheumatoid arthritis (RA) by conventional echocardiography and two-dimensional speckle tracking imaging (2D-STI). We enrolled 46 RA patients with a duration of < 5 years as Group I, 40 RA patients with a duration of ≥ 5 years as Group II, and 40 normal subjects as the control group. Conventional echocardiography was conducted to measure traditional parameters. The LA strain during reservoir phase (LASr), LA strain during conduit phase (LAScd), LA strain during contraction phase (LASct), and LA global longitudinal strain (LAGLS) were obtained from 2D-STI. Related ultrasound results were compared. The LASct was significantly higher in Group I than in control group (P < 0.05). The LASr, LAScd, and LAGLS were significantly lower in Group I than in control group (all P < 0.05). The LASr, LAScd, LASct, and LAGLS were significantly lower in Group II than in control group and Group I (all P < 0.05). The function of LA impaired in RA patients, and the impairment aggravated with the clinical course of RA patients. 2D-STI technology can early and accurately evaluate the LA function of RA patients by evaluating LASr, LAScd, LASct, and LAGLS.


Assuntos
Artrite Reumatoide/fisiopatologia , Função do Átrio Esquerdo , Ecocardiografia/métodos , Átrios do Coração/patologia , Interpretação de Imagem Assistida por Computador/métodos , Ultrassonografia/métodos , Adulto , Artrite Reumatoide/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Átrios do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade
20.
Molecules ; 26(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34641582

RESUMO

The accumulation of amyloid plaques, or misfolded fragments of proteins, leads to the development of a condition known as amyloidosis, which is clinically recognized as a systemic disease. Amyloidosis plays a special role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease, and rheumatoid arthritis (RA). The occurrence of amyloidosis correlates with the aging process of the organism, and since nowadays, old age is determined by the comfort of functioning and the elimination of unpleasant disease symptoms in the elderly, exposure to this subject is justified. In Alzheimer's disease, amyloid plaques negatively affect glutaminergic and cholinergic transmission and loss of sympathetic protein, while in RA, amyloids stimulated by the activity of the immune system affect the degradation of the osteoarticular bond. The following monograph draws attention to the over-reactivity of the immune system in AD and RA, describes the functionality of the blood-brain barrier as an intermediary medium between RA and AD, and indicates the direction of research to date, focusing on determining the relationship and the cause-effect link between these disorders. The paper presents possible directions for the treatment of amyloidosis, with particular emphasis on innovative therapies.


Assuntos
Envelhecimento/metabolismo , Doença de Alzheimer/fisiopatologia , Amiloidose/fisiopatologia , Artrite Reumatoide/fisiopatologia , Sistema Imunitário/fisiopatologia , Doença de Parkinson/fisiopatologia , Placa Amiloide/fisiopatologia , Barreira Hematoencefálica/fisiopatologia , Encéfalo/metabolismo , Citocinas/metabolismo , Humanos
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